In situ mechanochemical synthesis of nitrones followed by 1,3-dipolar cycloaddition: a catalyst-free, “green” route to cis-fused chromano[4,3-c]isoxazoles

Abstract

An efficient and catalyst-free method for the synthesis of cis-fused chromano[4,3-c]isoxazoles via intramolecular 1,3-dipolar nitrone cycloaddition involving hand-grinding in a mortar-pestle has been developed. The mechanochemical agitation was sufficient for dehydrative nitrone formation by condensation of various O-allyl salicylaldehyde derivatives and alkyl/aryl hydroxylamines. The corresponding nitrones undergo intramolecular 1,3-dipolar cycloaddition leading to regioselective formation of cis-fused tetrahydrochromeno[4,3-c]isoxazole derivatives in high yields. The key features of this new method are cleaner reaction profiles, catalyst-free conditions, high yields, and short reaction times.